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Cancer Discov. 2018 Oct;8(10):1258-1269. doi: 10.1158/2159-8290.CD-18-0743. Epub 2018 Aug 28.

In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma.

Author information

1
Stanford University Hospital and Clinics, Division of Oncology, Stanford, California.
2
University of Rochester Medical Center, Rochester, New York.
3
Washington University School of Medicine, Siteman Cancer Center, St. Louis, Missouri.
4
Feinberg School of Medicine, Northwestern University and the Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois.
5
Stanford University Hospital and Clinics, Department of Radiation Oncology, Stanford, California.
6
Dynavax Technologies Corporation, Berkeley, California.
7
Stanford University Hospital and Clinics, Division of Oncology, Stanford, California. levy@stanford.edu.

Abstract

This multicenter phase I/II clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. Twenty-nine enrolled patients received 4 Gy of radiation followed by 5 weekly intratumoral injections of SD-101 at a single tumor site. No treatment-related grade 4 or serious adverse events occurred. Nearly all patients had tumor reduction at their treated site. More importantly, 24 patients had tumor reduction at their nontreated sites, with 5 patients achieving a partial response and one achieving a complete response. Treatment-related increases of CD8+ and CD4+ effector T cells and decreases of T follicular helper and T regulatory cells (Treg) were observed in the tumor microenvironment. Low pretreatment levels of CD4+ Tregs, proliferating CD8+ T cells, and Granzyme B+ CD8+ T cells were associated with favorable outcomes. Intratumoral SD-101 in combination with low-dose radiation is well tolerated and results in regression of both treated and untreated sites of disease.Significance: In situ vaccination with the TLR9 agonist SD-101, along with low-dose radiation, was safe and induced systemic responses in patients with indolent lymphoma. Low levels of CD4+ Tregs, proliferating CD8+ T cells, and Granzyme B+ CD8+ T cells in the tumor microenvironment predicted favorable response to treatment. Cancer Discov; 8(10); 1258-69. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1195.

PMID:
30154192
PMCID:
PMC6171524
[Available on 2019-10-01]
DOI:
10.1158/2159-8290.CD-18-0743

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